Intercostal Nerve Cryoanalgesia Versus Thoracic Epidural Analgesia in Lung Transplantation: A Retrospective Single-Center Study

Optimal pain control after a clamshell incision is an essential part of postoperative recovery. In this manuscript, we retrospectively reviewed a series of lung transplant patients who underwent either thoracic epidural placement or cryoanalgesia.

Our findings suggest that intercostal nerve blockade with cryoanalgesia in patients who undergo bilateral lung transplantation via clamshell incision is safe and has equivalent effectiveness compared to TEA. There was no statistically significant difference between the cohorts in pain score and total opioid use through POD7. While we did not measure pain scores or opioid use beyond POD7, it is notable that Cryo lasts much longer than 7 days (up to several months) and can provide postoperative pain control for the majority of a patient’s recovery. In contrast, TEA is placed for a limited period only, and pain recurs after catheter removal.

We observed several potential advantages of Cryo over TEA in this patient population. For one, Cryo can be utilized in most (in this series in all) patients, with exceptions including patients with exposed intercostal nerves or thickened pleural scars. However, TEA is limited to those with “standard” postoperative recoveries. In fact, epidural placement in our study was delayed beyond POD1 in one-third of the TEA subjects, which can translate into more systemic opioid use prior to epidural placement. The predominant reason for delay was need for postoperative ECMO, as the anticoagulation required for ECMO was a contraindication to epidural placement. Some degree of primary graft dysfunction occurs in about 80% of transplant recipients, with 16% having severe (grade 3) PGD [20]. Between 5% and 10% of patients with severe PGD will require ECMO as a bridge to recovery [21,22,23]; thus, a sizeable cohort of patients will have delayed epidural placement in anticipation of ECMO need in the near future. Other reasons for delay in placement included clinical instability unrelated to ECMO and unavailability of the pain specialist. Although there are centers that place TEA preoperatively [3], we utilize ECMO with anticoagulation intraoperatively on nearly all bilateral lung implantations, and it is our practice to place TEA postoperatively in the ICU prior to extubation. This practice allows for thorough post-transplant evaluation of the patient, including neurologic and hemodynamic status as well as risk of primary graft dysfunction. Cryo, in contrast, was successfully administered in all patients as it was independent of the clinical state and availability of the pain specialist to place the epidural. At our institution, it takes 20 min to ablate bilateral interspaces, and is performed either after native lung/hilar dissection while waiting for the arrival of the donor organs in the operating room or during ECMO wean post-implantation allowing controlled reperfusion of the allografts. As such, administration of cryoanalgesia does not prolong operative time. Second, TEA can be associated with analgesic-specific morbidity, defined as adverse events directly attributable to analgesia. While analgesic-specific morbidity was overall minimal in our study, two TEA patients experienced hemodynamic instability following a test bolus of ropivacaine requiring code measures. Of note, these patients had been clinically stable and received the standard dose and concentration of ropivacaine bolus. Life-threatening hemodynamic instability is rare, and TEA is more commonly associated with modest hypotension that can confound the clinical picture in these complex patients [2]. TEA can also be complicated by traumatic hematoma, infection with epidural abscess, and catheter migration necessitating replacement with repeat procedure [1,2,3,4,5,6]. TEA patients in our study did not experience any of these insertion site complications. In contrast to TEA, there were no observable complications associated with Cryo. While a possible association of Cryo with neuropathic pain has been previously reported [12], no Cryo patients in the study time period experienced neuropathic pain requiring pharmacologic intervention. It is possible that our findings are due to differing and improving equipment and techniques.

Beyond the aforementioned complications, TEA is labor intensive and detracts from managing more pertinent clinical issues. TEA requires 24-h monitoring and care by pain specialists, pharmacists, and nurses. In our study, over a third of the TEA patients required modification of the infusion to maintain adequate analgesia. In contrast, Cryo is an efficient analgesic method with a one-time application, which does not require further monitoring or care. While we were not able to perform direct cost comparison between TEA and Cryo, it is very likely that the costs of the drug (ropivacaine and/or fentanyl), its preparation by the pharmacist, and the need for daily monitoring by staff (both nursing and pain specialists) make TEA a much more costly venture than a single-use cryoablation probe and procedure.

Four Cryo patients did require TEA for pain control. Three of these patients were among our very first Cryo patients, and they received TEA out of concern for potential inadequacy of Cryo. In retrospect, these patients likely could have been maintained with Cryo alone. Regardless, we did alter our technique to ablate five interspaces as opposed to four on each side to cover the chest tube insertion site, and perhaps our improved subsequent outcomes were due to this modification. We found that the Cryo patients who required TEA did not influence the overall results of our study.

This retrospective study has several limitations. Over the 2 years of the study period, our lung transplantation program had a significant increase in emergency evaluation and transplantation of patients with acute on chronic respiratory decompensation. In fact, prior to the institution of Cryo in July 2017, 29.7% of transplant patients were in the ICU prior to surgery, compared to 35.0% after July 2017 [24]. As such, the TEA and Cryo cohorts had substantial differences: Cryo patients were sicker, had higher lung allocation score, more tracheostomies, and longer hospital stays post-transplant. Although we adjusted for confounding characteristics, there may still be unmeasured variables that could alter the findings. Next, our database only contains opioid use and pain scores through POD7. As nerve regeneration after Cryo occurs over weeks to months, there may be differences in these outcomes that emerge with time between the techniques. We did not compare Cryo to other regional analgesics, such as liposomal bupivacaine injection, because of the latter’s limited duration and potential altered pharmacokinectics in lung transplant recipients at risk of kidney and/or hepatic dysfunction from immunosuppressants and prophylactic antimicrobials. In addition, we recognize the inherent limitations given our small sample size. While we believe our data supports the conclusion that Cryo and TEA have equivalent postoperative analgesic effects, further studies are necessary prior to drawing definitive conclusions regarding differences in complications and long-term outcomes. Despite these limitations, this study represents the first evaluation of Cryo in patients undergoing lung transplantation via a clamshell incision and demonstrates its safety and effectiveness.

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